Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis.
Leptin, a recently-discovered hormonal product of the obese (ob) gene, circulates in the blood at levels paralleling those of fat reserves and regulates satiety. Although noninsulin-dependent diabetics are insulin-resistant and have greater levels of leptin than normal subjects, little evidence existed previously to support the notion that leptin can influence insulin action, particularly in the ovary. Therefore, we tested the hypothesis that leptin signals metabolic information to the reproductive system by directly affecting insulin-induced thecal cell function. Thecal cells from bovine ovarian follicles were cultured for 2 days in the presence of 10% fetal calf serum, and then cultured for an additional 2 days in serum-free medium with added hormones. Doses of 10 to 300 ng/ml of leptin increased (p < 0.05) insulin-induced proliferation of thecal cells by 8% to 16%. In contrast, leptin blocked (p < 0.05) insulin-induced progesterone and androstenedione production by thecal cells. Insulin and leptin had no effect (p > 0.10) on thecal cell viability. Specific high-affinity, low-capacity binding of 125I-leptin was also demonstrable in thecal cells. Furthermore, leptin did not compete for [125I]insulin binding to thecal cells, whereas unlabeled insulin did. In conclusion, leptin can directly attenuate insulin-induced steroidogenesis of thecal cells while stimulating proliferation of the same cell type. This inhibitory effect of leptin on steroidogenesis does not appear to be mediated through inhibiting binding of insulin to its receptor but rather appears to be mediated through leptin binding to its own receptor. These results provide evidence for a role of leptin as a metabolic signal to the reproductive system via direct action in the ovary.
Spicer
L J
LJ
Department of Animal Science, Oklahoma State University, Stillwater 74078, USA.
Francisco
C C
CC
D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D020738:Leptin; D009765:Obesity; D011374:Progesterone / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D013256:Steroids / Q000096:biosynthesis*; D013799:Theca Cells / Q000187:drug effects* / Q000378:metabolism*
D007328:Insulin; D020738:Leptin; D011506:Proteins; D013256:Steroids; D000735:Androstenedione; D011374:Progesterone